The prevalence of obesity in children and young adults has increased dramatically in recent years. However, conventional treatment has had poor long-term effectiveness. The short-term goal of this application is to provide David Ludwig, MD, PhD, a nationally-recognized expert in childhood obesity, protected time to mentor junior investigators in patient-oriented research. Dr. Ludwig has a track record of high quality scientific publications, completed and current NIH grants, and mentoring. He is founding director of one of the country's oldest and largest pediatric obesity clinics, and co-director of a new, hospital-wide translational research program in pediatric obesity. The long-term scientific goal of this project is to examine the effects of dietary composition on hormonal response, metabolism, body weight regulation and risk for type 2 diabetes and cardiovascular disease. The proposed research includes three Specific Aims: 1) a feeding study comparing low fat, very low carbohydrate and low glycemic load diets after weight loss;2) a 2- year RCT of diet in the treatment of obesity in children;and 3) a 2-year RCT examining the effects of reducing sugar-sweetened beverage consumption on body weight in obese adolescents. The long-term mentoring goal of this project is to help train clinical scientists in the areas of pediatric obesity and nutrition by providing opportunities at all levels (undergraduate, medical student, resident, fellow and junior faculty) to work on state-of-the-art clinical research ranging from mechanistically oriented feeding studies to environmentally-based interventions. The research environment is ideal to support these goals, including the presence of a General Clinical Research Center at Children's Hospital Boston and a K30 training program at Harvard Medical School (with an application for CTSC pending), outstanding access to patients and clinical materials, and an exciting intellectual environment with numerous clinical and basic investigators working in related areas. PUBLIC HEALTH RELEVANCE: Childhood obesity threatens to shorten life-expectancy in the US and cost tax-payers many trillions of dollars over the next few decades. To prevent this potentially catastrophic fiscal and human toll, novel approaches to the prevention and treatment of obesity are needed, and the next generation of clinical scientists with expertise in pediatric obesity must be trained. This application will support the ability of Dr. Ludwig, a midcareer clinician-scientist with an outstanding track record, to contribute in these two areas.